Hachimijiogan, a traditional herbal medicine, modulates adipose cell function and ameliorates diet-induced obesity and insulin resistance in mice.

(HJG) has originally been used to ameliorate a variety of symptoms associated with low ambient temperatures. However, its pharmacological action in metabolic organs remains unclear. We hypothesized that HJG may modulate metabolic function and have a potential therapeutic application to metabolic diseases.

Gsk-3-Mediated Proteasomal Degradation of ATF4 Is a Proapoptotic Mechanism in Mouse Pancreatic β-Cells.

Endoplasmic reticulum (ER) stress is a key pathogenic factor in type 1 and 2 diabetes. Glycogen synthase kinase 3 (Gsk-3) contributes to β-cell loss in mice. However, the mechanism by which Gsk-3 leads β-cell death remains unclear.

Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes.

Objective: To elucidate the pathogenesis of postpancreatectomy diabetes mellitus (PPDM).

Research Design And Methods: Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) ( = 20) or distal pancreatectomy (DP) ( = 28) were included. A 75-g oral glucose tolerance test was performed every 6 months.

Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes.

Dedifferentiation has been implicated in β cell dysfunction and loss in rodent diabetes. However, the pathophysiological significance in humans remains unclear. To elucidate this, we analyzed surgically resected pancreatic tissues of 26 Japanese subjects with diabetes and 11 nondiabetic subjects, who had been overweight during adulthood but had no family history of diabetes.

Activation of GLP-1 receptor signalling alleviates cellular stresses and improves beta cell function in a mouse model of Wolfram syndrome.

Aims/hypothesis: Loss of functional beta cells results in a gradual progression of insulin insufficiency in Wolfram syndrome caused by recessive WFS1 mutations. However, beta cell dysfunction in Wolfram syndrome has yet to be fully characterised, and there are also no specific treatment recommendations. In this study, we aimed to characterise beta cell secretory defects and to examine the potential effects of a glucagon-like peptide-1 (GLP-1) receptor agonist on diabetes in Wolfram syndrome.

Interorgan Crosstalk Contributing to -Cell Dysfunction.

Type 2 diabetes mellitus (T2DM) results from pancreatic -cell failure in the setting of insulin resistance. In the early stages of this disease, pancreatic -cells meet increased insulin demand by both enhancing insulin-secretory capacity and increasing -cell mass. As the disease progresses, -cells fail to maintain these compensatory responses.

Sequential cleavage of insulin receptor by calpain 2 and γ-secretase impairs insulin signalling.

Aims/hypothesis: Soluble insulin receptor (sIR), the ectodomain of the insulin receptor (IR), has been detected in human plasma and its concentration paralleled that of blood glucose. We have previously developed an in vitro model using HepG2 liver-derived cells, which mimics changes in sIR levels in plasma from diabetic patients and shows that calcium-dependent proteases cleave IR extracellularly (a process known as shedding). The present study aimed to reveal the mechanisms of IR cleavage.